It is important that medical devices are biocompatible since most medical devices interface with biological tissues during use. Therefore, medical devices are preferred to be prepared from biocompatible materials. More specifically, the ideal materials for medical devices should satisfy at least the following requirements: (1) conformable, i.e., conform to the biological structure without inducing detrimental stress, (2) robust, i.e., withstand handling during fabrication and implantation, and (3) chemically inert to body tissue and body fluids. However, conventional materials used for the construction of medical devices, such as stainless steel and other alloys, not only are physically rigid, but also cause inflammatory reactions or other side effects when interfacing with biological tissues.
To overcome these problems, synthetic polymeric materials, including both biodegradable and non-biodegradable polymers, have been widely used to fabricate medical devices. Common biodegradable polymers include polylactide (PLA) polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA), polycaprolactone (PCL), polyphosphoesters (PPE), polyorthoesters, polyanhydrides, polyphosphazene, poly(esteramide) (PEA), and copolymers and mixtures thereof. Non-biodegradable polymers are also known as nonabsorbable polymers. Common nonabsorbable polymeric materials include, but are not limited to: silicone elastomers, polyutheranes, polymethyl methacrylate, Dacron®, Teflon®, and derivatives thereof. However, these polymeric materials are not radio-opaque. Consequently, medical devices made from these polymers cannot be visualized by means of radiographic imaging. The ability to see the radiographic image of a medical device being used in, or implanted within, the body is very important since radiographic imaging provides a physician the ability to monitor and adjust the medical device during operation. For some medical implant applications, X-ray visibility is mandatory.
To achieve desirable radio-opacity in the polymeric materials used for medical implants, one conventional method utilizes inorganic radiographic contrasting agents, such as barium sulfate, zirconium dioxide, or bismuth halides as additives or fillers in the polymeric material to form a radio-opaque polymeric matrix. However, these inorganic agents do not mix well with polymeric materials and may cause phase separation or even clumps in the radio-opaque polymeric matrix. The phase separation problem is further aggravated since high concentrations (around 10%, and often times 20-30% by weight) of these inorganic radiographic contrasting agents are routinely used to obtain the required radio-opacity. The incompatibility between the polymeric and inorganic phases compromises the physicomechanical properties (e.g., lubricity and robustness) of the polymer matrix. Another disadvantage of using inorganic radiographic contrasting agents is the leach-out of these inorganic agents from the radio-opaque polymeric matrix, which adversely compromises the mechanical strength of the polymeric material.
An alternative approach to introduce radio-opacity into polymeric materials is to synthesize polymers having covalently bound bromine or iodine atoms that may produce a radiographic contrasting effect (See U.S. Pat. No. 6,426,145). One radio-opaque composition of the prior art comprises a polymer having a non-leachable radio-opaque moiety covalently attached to the polymer (See U.S. Pat. No. 6,599,448), wherein the non-leachable radio-opaque moiety includes halogen substituted aromatic groups. The prior art has also disclosed a radio-opaque polymeric material comprising a diphenol-based monomer unit substituted with at least one bromine or iodine atom (See U.S. Pat. No. 6,852,308). However, preparations of these prior art radio-opaque polymers require synthesis of radiographic contrasting monomer units, which may increase the technical complexity and production cost.
Thus, there remains a need for a radiographic contrasting agent that is compatible with polymeric materials and provides enhanced contrasting intensity as well.